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J Steroid Biochem Mol Biol. 2014 Oct;144 Pt A:228-31. doi: 10.1016/j.jsbmb.2013.10.015. Epub 2013 Oct 28.

Regulation of the calcium-sensing receptor expression by 1,25-dihydroxyvitamin D3, interleukin-6, and tumor necrosis factor alpha in colon cancer cells.

Author information

1
Department of Pathophysiology and Allergy Research, Medical University of Vienna, Währinger Gürtel 18-20, Vienna, Austria. Electronic address: irfete.fetahu@meduniwien.ac.at.
2
Department of Pathophysiology and Allergy Research, Medical University of Vienna, Währinger Gürtel 18-20, Vienna, Austria. Electronic address: doris.hummel@meduniwien.ac.at.
3
Department of Pathophysiology and Allergy Research, Medical University of Vienna, Währinger Gürtel 18-20, Vienna, Austria. Electronic address: teresa.manhardt@meduniwien.ac.at.
4
Department of Pathophysiology and Allergy Research, Medical University of Vienna, Währinger Gürtel 18-20, Vienna, Austria. Electronic address: abhishek.aggarwal@meduniwien.ac.at.
5
Department of Internal Medicine III, Medical University of Vienna, Währinger Gürtel 18-20, Vienna, Austria. Electronic address: sabina.baumgartner-parzer@meduniwien.ac.at.
6
Department of Pathophysiology and Allergy Research, Medical University of Vienna, Währinger Gürtel 18-20, Vienna, Austria. Electronic address: enikoe.kallay@meduniwien.ac.at.

Abstract

Anti-proliferative effects of calcium in the colon are mediated, at least in part, via the calcium-sensing receptor (CaSR), a vitamin D target gene. The expression of CaSR decreases during colorectal tumor progression and the mechanisms regulating its expression are poorly understood. The CaSR promoter harbors vitamin D elements responsive to 1,25-dihydroxyvitamin D3 (1,25D3) and NF-κB, STAT, and SP1 binding sites accounting for responsiveness to proinflammatory cytokines. Therefore, in the current study we investigated the impact of 1,25D3, tumor necrosis factor alpha (TNFα), and interleukin (IL)-6 on CaSR expression in a differentiated (Caco2/AQ) and in a moderately differentiated (Coga1A) colon cancer cell line. 1,25D3 induced CaSR expression in both cell lines. Treatment with TNFα was accompanied by a 134-fold induction of CaSR in Coga1A (p<0.01). In Caco2/AQ cells the expression of CaSR was upregulated also by IL-6 (3.5-fold). Our data demonstrated transcriptional and translational activation of the CaSR by 1,25D3, TNFα, and IL-6 in a time- and cell line-dependent manner. This article is part of a Special Issue entitled '16th Vitamin D Workshop'.

KEYWORDS:

1,25-dihydroxyvitamin D(3); Calcium-sensing receptor; Colon cancer; Inflammation; Interleukin-6; Tumor necrosis factor alpha

PMID:
24176760
PMCID:
PMC4220008
DOI:
10.1016/j.jsbmb.2013.10.015
[Indexed for MEDLINE]
Free PMC Article

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